Framework Nucleic Acids in Nuclear Medicine Imaging: Shedding Light on Nano–Bio Interactions

Framework nucleic acids (FNAs) represent nanoscale oligonucleotide assemblies with unique physical, chemical, and biological properties that are different from their building blocks. Following simple Watson-Crick base-pairing rules, arbitrary DNA frameworks with diverse shapes, sizes, and dimensions can be prepared with high reproducibility and stability. The programmable assembly of nucleic acids into FNAs presents a highly controllable model for studies on nano-bio interactions and allows scrutiny of "nanostructure-activity relationships." Herein, we present an overview of recent progress with FNAs in the hope of deepening our understanding of nano-bio interfacing. We summarize the biological profiles and immune responses of various FNAs as functions of their shape, sizes, and surface charges. We then highlight recent efforts to apply FNAs for biomedical applications and discuss the challenges of FNAs for potential clinical translation. We believe that this Minireview can bring up-to-date information on FNAs and shed light on how their design may be harnessed for selective biomedical applications.